tbuckley/cabot-search huggingface dataset:
Interaction of Rifampin and Glucocorticoids
Authors: Gary A. Buffington
Journal: JAMA (1976)

Three renal transplant patients experienced progressive loss of renal allograft function during rifampin treatment for<i>Mycobacterium tuberculosis</i>. Previous studies have shown that rifampin causes induction of enzymes in hepatic microsomes that increase the catabolism of glucocorticoids. Evidence is presented that in our patients, the loss of renal allograft function during rifampin therapy was the result of decreased glucocorticoid effect presumably related to increased catabolism of the glucocorticoid drug they received. Thus, the adverse effects of rifampin on renal transplant function might be overcome by increasing the dose of glucocorticoid drug. (<i>JAMA</i>236:1958-1960, 1976)
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Authors: Laurel A Monticelli, Gregory F Sonnenberg, Michael C Abt, Theresa Alenghat, Carly G K Ziegler, Travis A Doering, Jill M Angelosanto, Brian J Laidlaw, Cliff Y Yang, Taheri Sathaliyawala, Masaru Kubota, Damian Turner, Joshua M Diamond, Ananda W Goldrath, Donna L Farber, Ronald G Collman, E John Wherry, David Artis
Journal: Nature Immunology (2011)
A New Treatment for Postherpetic Neuralgia
Authors: C. Peter N. Watson
Journal: New England Journal of Medicine (2000)

Postherpetic neuralgia is the most frequent and feared complication of herpes zoster, which is the most common neurologic illness in the United States.1 Data from the VZV (Varicella Zoster Virus) Research Foundation, in New York City, indicate that herpes zoster may occur in as many as 850,000 people in the United States each year. Postherpetic neuralgia, when defined as persistent pain occurring one month after the healing of the herpetic rash, affects about 10 percent of patients with herpes zoster. However, the incidence of postherpetic neuralgia is directly related to age. Up to 75 percent of people with herpes zoster . . .
Decrease in serum levels of markers of hepatic connective tissue turnover during and after treatment of chronic hepatitis B with interferon-α
Authors: Carlos J. Teran, Kevin D. Mullen, Jay H. Hoofnagle, Arthur J. McCullough
Journal: Hepatology (1994)

Interferon-α induces remission in 30% to 40% of patients with chronic hepatitis B, but its effect on hepatic connective tissue turnover has not been well documented. We studied the changes in serum procollagen III propeptide and laminin-P1 peptide (Lam-P1) in 33 patients with chronic hepatitis B (11 nontreated controls and 22 treated patients) during a 4-mo randomized trial of interferon-α. Liver biopsy specimens were obtained at the start of treatment and 12 mo later. Liver biochemical tests, procollagen III propeptide, laminin-P1 peptide and hepatitis B virus DNA polymerase were determined before treatment with interferon was begun (mo -3), at the initiation (0 time) and completion of treatment (mo 4) and also at 8, 12 and 18 mo. Treated patients were classified as “responders” and “nonresponders” on the basis of clearance of HBV e antigen from serum. There were no significant changes in the control group, whereas the responders had persistent decreases in ALT, AST, hepatitis B virus dna polymerase, procollagen III propeptide and laminin-P1 peptide. The nonresponders had transient ALT, AST and hepatitis B virus dna polymerase reductions that returned toward baseline levels during follow-up, but procollagen III propeptide and laminin-P1 peptide persisted below the baseline at mo 18. Significant correlations between procollagen III propeptide and laminin-P1 peptide with ALT, AST and liver histologic specimens were noted at baseline but not after 12 mo. Changes in procollagen III propeptide levels also correlated with changes in AST, ALT and liver histologic specimens. On the basis of logistic regression, neither markers of connective tissue turnover nor histology improved the accuracy of AST, ALT and hepatitis B virus dna polymerase for predicting response to interferon. We conclude that interferon treatment induces a persistent suppression in serum markers of hepatic connective tissue turnover in chronic hepatitis B patients independent of its effect on viral replication and hepatic necroinflammation. (Hepatology 1994;19:849-856.)
Congenital Bilateral Absence of the Vas Deferens
Authors: Arturo Anguiano
Journal: JAMA (1992)

<h3>Objective.</h3> —Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. <h3>Design.</h3> —We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. <h3>Setting.</h3> —All the patients presented to a male infertility clinic of a teaching hospital. <h3>Subjects.</h3> —Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. <h3>Results.</h3> —Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (<i>P</i>&lt;.001). Moreover, we have thus far determined that three of these 16 men are compound heterozygotes, one of whom has a mutation not previously described. Analyses continue on patients who have yet to yield a detectable mutation. <h3>Conclusions.</h3> —Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives. (<i>JAMA</i>. 1992;267:1794-1797)
End-Tidal Carbon Dioxide Monitoring During Cardiopulmonary Resuscitation
Authors: Arthur B. Sanders
Journal: JAMA (1989)

The effectiveness of ongoing cardiopulmonary resuscitation efforts is difficult to evaluate. Recent studies suggest that carbon dioxide excretion may be a useful noninvasive indicator of resuscitation from cardiac arrest. A prospective clinical study was done to determine whether end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation could be used as a prognostic indicator of resuscitation and survival. Thirty-five cardiac arrests in 34 patients were monitored with capnometry during cardiopulmonary resuscitation during a 1-year period. Nine patients who were successfully resuscitated had higher average end-tidal carbon dioxide partial pressures during cardiopulmonary resuscitation than 26 patients who could not be resuscitated (15±4 vs 7±5 mm Hg). The 3 patients who survived to leave the hospital had a higher average end-tidal carbon dioxide partial pressure than the 32 nonsurvivors (17 ± 6 vs 8 ± 5 mm Hg). All 9 patients who were successfully resuscitated had an average end-tidal carbon dioxide partial pressure of 10 mm Hg or greater. No patient with an average end-tidal carbon dioxide partial pressure of less than 10 mm Hg was resuscitated. Data from this prospective clinical trial indicate that findings from end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation are correlated with resuscitation from and survival of cardiac arrest. (<i>JAMA</i>. 1989;262:1347-1351)
Peripheral Nerve Block With Phenol in the Management of Spasticity
Authors: Ali A. Khalili
Journal: JAMA (1967)

After accurate isolation, 126 peripheral nerves were blocked with 2% or 3% phenol solutions in distilled water in 68 patients with severe spasticity of various causes. Seven nerve blocks were repeated. The period of effectiveness ranged from 2 to 743 days, with an average of 308 days. Paresthesia occurred following ten nerve blocks. Gain and loss of voluntary movement following the blocks were observed. Ease, simplicity, safety, therapeutic benefits, and economic advantages of peripheral nerve block with phenol warrant its more widespread use.
Does This Patient Have Community-Acquired Pneumonia?
Authors: Joshua P. Metlay, Wishwa N. Kapoor, Michael J. Fine
Journal: JAMA (1997)

Community-acquired pneumonia is an important cause of acute respiratory symptoms (eg, cough) in the ambulatory care setting. Distinguishing pneumonia from other causes of respiratory illnesses, such as acute bronchitis and upper respiratory tract infections, has important therapeutic and prognostic implications. The reference standard for diagnosing pneumonia is chest radiography, but it is likely that many physicians rely on the patient's history and their physical examination to diagnose or exclude this disease. A review of published studies of patients suspected of having pneumonia reveals that there are no individual clinical findings, or combinations of findings, that can rule in the diagnosis of pneumonia for a patient suspected of having this illness. However, some studies have shown that the absence of any vital sign abnormalities or any abnormalities on chest auscultation substantially reduces the likelihood of pneumonia to a point where further diagnostic evaluation may be unnecessary. This article reviews the literature on the appropriate use of the history and physical examination in diagnosing community-acquired pneumonia.
Double-blind Study of Lorazepam and Diazepam in Status Epilepticus
Authors: llo E. Leppik
Journal: JAMA (1983)

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted. (<i>JAMA</i>1983;249:1452-1454)
Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease
Authors: Sebastiaan De Schepper, Judy Z. Ge, Gerard Crowley, Laís S. S. Ferreira, Dylan Garceau, Christina E. Toomey, Dimitra Sokolova, Javier Rueda-Carrasco, Sun-Hye Shin, Jung-Seok Kim, Thomas Childs, Tammaryn Lashley, Jemima J. Burden, Michael Sasner, Carlo Sala Frigerio, Steffen Jung, Soyon Hong
Journal: Nature Neuroscience (2023)

Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell-cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD.
Prevalence of smoldering multiple myeloma based on nationwide screening
Authors: Sigrún Thorsteinsdóttir, Gauti K. Gíslason, Thor Aspelund, Sæmundur Rögnvaldsson, Jón Þórir Óskarsson, Guðrún Á Sigurðardóttir, Ásdís R. Þórðardóttir, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Elías Eyþórsson, Ásbjörn Jónsson, Oscar Berlanga, Malin Hultcrantz, Brian G. M. Durie, Thorvardur J. Löve, Stephen Harding, Ola Landgren, Sigurður Y. Kristinsson
Journal: Nature Medicine (2023)
Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice
Authors: Steven S. Hou, Joyce Yang, Jeong Heon Lee, Yeseo Kwon, Maria Calvo-Rodriguez, Kai Bao, Sung Ahn, Satoshi Kashiwagi, Anand T. N. Kumar, Brian J. Bacskai, Hak Soo Choi
Journal: Nature Biomedical Engineering (2023)
COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Juan Ignacio Ruiz, Maria Angeles Lopez-Olivo, Yimin Geng, Maria E Suarez-Almazor
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE. Methods The objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models. Results Overall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low. Conclusion COVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.
SpliceVault predicts the precise nature of variant-associated mis-splicing
Authors: Ruebena Dawes, Adam M. Bournazos, Samantha J. Bryen, Shobhana Bommireddipalli, Rhett G. Marchant, Himanshu Joshi, Sandra T. Cooper
Journal: Nature Genetics (2023)

Abstract Even for essential splice-site variants that are almost guaranteed to alter mRNA splicing, no current method can reliably predict whether exon-skipping, cryptic activation or multiple events will result, greatly complicating clinical interpretation of pathogenicity. Strikingly, ranking the four most common unannotated splicing events across 335,663 reference RNA-sequencing (RNA-seq) samples (300K-RNA Top-4) predicts the nature of variant-associated mis-splicing with 92% sensitivity. The 300K-RNA Top-4 events correctly identify 96% of exon-skipping events and 86% of cryptic splice sites for 140 clinical cases subject to RNA testing, showing higher sensitivity and positive predictive value than SpliceAI. Notably, RNA re-analyses showed we had missed 300K-RNA Top-4 events for several clinical cases tested before the development of this empirical predictive method. Simply, mis-splicing events that happen around a splice site in RNA-seq data are those most likely to be activated by a splice-site variant. The SpliceVault web portal allows users easy access to 300K-RNA for informed splice-site variant interpretation and classification.
Association of the Chantix Recall With US Prescribing of Varenicline and Other Medications for Nicotine Dependence
Authors: Adam Edward Lang, Urvashi Patel, Jonathan Fitzpatrick, Tiffany Lee, Margo McFarland, Chester B. Good
Journal: JAMA Network Open (2023)

This cross-sectional study evaluates the association between the 2021 varenicline tartrate recall and prescribing of varenicline and other medications for nicotine dependence in a large US national patient cohort.
Intratumoral IFN-γ or topical TLR7 agonist promotes infiltration of melanoma metastases by T lymphocytes expanded in the blood after cancer vaccine
Authors: Christine A Tran, Kevin T Lynch, Max O Meneveau, Priya Katyal, Walter C Olson, Craig L Slingluff,
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune-mediated melanoma regression relies on melanoma-reactive T cells infiltrating tumor. Cancer vaccines increase circulating melanoma-reactive T cells, but little is known about vaccine-induced circulating lymphocytes (viCLs) homing to tumor or whether interventions are needed to enhance infiltration. We hypothesized that viCLs infiltrate melanoma metastases, and intratumoral interferon (IFN)-γ or Toll-like receptor 7 (TLR7) agonism enhances infiltration. Methods Patients on two clinical trials (Mel51 ( NCT00977145 ), Mel53 ( NCT01264731 )) received vaccines containing 12 class I major histocompatibility complex-restricted melanoma peptides (12MP). In Mel51, tumor was injected with IFN-γ on day 22, and biopsied on days 1, 22, and 24. In Mel53, dermal metastases were treated with topical imiquimod, a TLR7 agonist, for 12 weeks, and biopsied on days 1, 22, and 43. For patients with circulating T-cell responses to 12MP by IFN-γ ELISpot assays, DNA was extracted from peripheral blood mononuclear cells (PBMCs) pre-vaccination and at peak T-cell response, and from tumor biopsies, which underwent T-cell receptor sequencing. This enabled identification of clonotypes induced in PBMCs post-vaccination (viCLs) and present in tumor post-vaccination, but not pre-vaccination. Results Six patients with T-cell responses post-vaccination (Mel51 n = 4, Mel53 n = 2) were evaluated for viCLs and vaccine-induced tumor infiltrating lymphocytes (viTILs). All six patients had viCLs, five of whom were evaluable for viTILs in tumor post-vaccination alone. Mel51 patients had viTILs identified in day 22 tumors, post-vaccination and before IFN-γ (median = 2, range = 0–24). This increased in day 24 tumors after IFN-γ (median = 30, range = 4–74). Mel53 patients had viTILs identified in day 22 tumors, post-vaccination plus imiquimod (median = 33, range = 2–64). Three of five evaluable patients across both trials had viTILs with vaccination alone. All five had enhancement of viTILs with tumor-directed therapy. viTILs represented 0.0–2.9% of total T cells after vaccination alone, which increased to 0.6–8.7% after tumor-directed therapy. Conclusion Cancer vaccines induce expansion of new viCLs, which infiltrate melanoma metastases in some patients. Our findings identify opportunities to combine vaccines with tumor-directed therapies to enhance T-cell infiltration and T cell-mediated tumor control. These combinations hold promise in improving the therapeutic efficacy of antigen-specific therapies for solid malignancies.
The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism
Authors: Elisangela Bressan, Xylena Reed, Vikas Bansal, Elizabeth Hutchins, Melanie M. Cobb, Michelle G. Webb, Eric Alsop, Francis P. Grenn, Anastasia Illarionova, Natalia Savytska, Ivo Violich, Stefanie Broeer, Noémia Fernandes, Ramiyapriya Sivakumar, Alexandra Beilina, Kimberley J. Billingsley, Joos Berghausen, Caroline B. Pantazis, Vanessa Pitz, Dhairya Patel, Kensuke Daida, Bessie Meechoovet, Rebecca Reiman, Amanda Courtright-Lim, Amber Logemann, Jerry Antone, Mariya Barch, Robert Kitchen, Yan Li, Clifton L. Dalgard, Patrizia Rizzu, Dena G. Hernandez, Brooke E. Hjelm, Mike Nalls, J. Raphael Gibbs, Steven Finkbeiner, Mark R. Cookson, Kendall Van Keuren-Jensen, David W. Craig, Andrew B. Singleton, Peter Heutink, Cornelis Blauwendraat
Journal: Cell Genomics (2023)

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.
Movement Optimization for a Cyborg Cockroach in a Bounded Space Incorporating Machine Learning
Authors: Mochammad Ariyanto, Chowdhury Mohammad Masum Refat, Kazuyoshi Hirao, Keisuke Morishima
Journal: Cyborg and Bionic Systems (2023)

Cockroaches can traverse unknown obstacle-terrain, self-right on the ground and climb above the obstacle. However, they have limited motion, such as less activity in light/bright areas and lower temperatures. Therefore, the movement of the cyborg cockroaches needs to be optimized for the utilization of the cockroach as a cyborg insect. This study aims to increase the search rate and distance traveled by cockroaches and reduce the stop time by utilizing automatic stimulation from machine learning. Multiple machine learning classifiers were applied to classify the offline binary classification of the cockroach movement based on the inertial measuring unit input signals. Ten time-domain features were chosen and applied as the classifier inputs. The highest performance of the classifiers was implemented for the online motion recognition and automatic stimulation provided to the cerci to trigger the free walking motion of the cockroach. A user interface was developed to run multiple computational processes simultaneously in real time such as computer vision, data acquisition, feature extraction, automatic stimulation, and machine learning using a multithreading algorithm. On the basis of the experiment results, we successfully demonstrated that the movement performance of cockroaches was importantly improved by applying machine learning classification and automatic stimulation. This system increased the search rate and traveled distance by 68% and 70%, respectively, while the stop time was reduced by 78%.